Maybe I can give you some information.
I'm using Lutris as Wine client and wine 2.16-staging 64bit version (with dotnet40 installed over winetricks). I have downloaded and installed a clean Steam and a clean release version of DOS2, but I can't run game over Steam client, I need to run it directly from "steamapps" folder.
I'm on Ubuntu 16.04 and I can't remember, that I did any special wine configuration changes.
I have NVidia 980 GTX and I think, I have NVIDIA drivers for it.
When I start the game from Steam, it fails to install dependencies. .NET Framework 3.5 is the problem I think, I tried to install it manually too, but it also fails when installation process tries to download some files from the internet (I guess it's some Wine bug or no support issue, could be also related to 64bit, I don't know exactly). So I gave up from .NET Framework and tried to install Mono just get around .NET Framework dependency and I still had the same problem with dependency installation by Steam. After that, I tried to run game manually and it worked.
What I have noticed additionally when I start the game over Steam client, it goes over dependency installation and then it tries to start the game - and I see next to game: DOS2 - Running, after that DOS2 - Syncing - and that's it.
I would like to collect all problems + solutions/workarounds in this post: http://larian.com/forums/ubbthreads.php?ubb=showflat&Number=614453#Post614453